Cognitive assessment during the phases of a spontaneous migraine: a prospective cohort study.

INTRODUCTION: Cognitive symptoms are reported commonly throughout all phases of a migraine; however, there is a paucity of objective cognitive profiling. Previous studies have been limited by practice effect, and variable populations. METHODS: Participants completed 1 month of daily testing with a computerised cognitive battery involving a simple reaction (SRT), choice reaction (CRT) and a working memory test (WM). Results were correlated with their diary to identify interictal scores, and scores during each phase of a migraine, and non-migraine headache days. RESULTS: A total of 16 patients with episodic migraine participated. During the headache phase of a migraine, responses to SRT, CRT and WM tasks were significantly slower and less accurate than interictally. During the postdrome, WM task performance was slower and less accurate. Non-migraine headache days were not associated with significant change. CONCLUSION: The headache and postdromal phase of a migraine day was associated with objective evidence of cognitive dysfunction in patients with episodic migraine.

Interventional treatments.

In migraine, when patients have failed medication management or are unable to be treated with systemic medications, minimally invasive interventions can be options used to provide pain relief. The type of intervention depends on the pain location, associated clinical features, clinical context, medical comorbidities, and response to prior injections. Interventions can vary from bedside peripheral nerve blocks to fluoroscopically guided interventions. Growing evidence is supporting the use of interventions in migraine, and judicious use can improve clinical outcomes.

Relationship of migraine and other forms of chronic pain.

The disability of migraine, a highly prevalent condition, is worsened by a second comorbid chronic pain condition. There is evidence of a relationship between migraine and several visceral pain conditions including irritable bowel syndrome, endometriosis, and dysmenorrhoea, as well as nonvisceral conditions including temporomandibular dysfunction, fibromyalgia, and lower back pain. While the mechanisms linking these conditions are inadequately surmised, a two-way relationship between migraine and these comorbidities likely exists. The progression and chronification of migraine is associated with peripheral and central sensitization, which may predispose to other conditions. Conversely, aspects of the mechanism of each comorbid condition may promote further migraine attacks. This chapter introduces each comorbidity, briefly summarizes the existing evidence, and discusses implications for treatment.

Pathology of MRI and second-look ultrasound detected multifocal breast cancer.

INTRODUCTION: Targeted second-look ultrasound (US) is often performed following MRI of the breast to determine if an MRI-detected lesion is visible on US and thus amenable to US-guided biopsy. This study aimed to assess the pathology of lesions detected and biopsied on the second-look US. In particular, for multifocal cancers, whether the pathology of additional lesions detected by second-look US is different to the index lesion. METHODS: Multicentre single-institution retrospective study of 300 consecutive cases of second-look US biopsies from August 2017 to April 2022 was performed, with their histopathology and imaging characteristics recorded. For multifocal cancers, Wilcoxon Signed Ranks Tests were used to compare differences between the index and additional lesions in the histopathology category (i.e., high-risk benign, precursor or malignant) and BRE grade. RESULTS: 69 multifocal cancers were detected. For the purposes of this study, additional lesions were considered more invasive if they were of a higher histopathological category or BRE grade, or demonstrated lymphovascular invasion when the primary lesion did not. 15/69 additional lesions were not seen on the initial mammogram/tomography or ultrasound, seen on subsequent MRI and second look US, and were less invasive than the index lesion. 3/69 additional lesions were more invasive than their index lesions. Wilcoxon Signed Ranks test showed additional lesions were of either similar or lesser invasiveness compared to index lesions (z= -3.207, p = 0.001) in the histopathological category, and the same or lower BRE grade (z= -2.972, p = 0.003). CONCLUSION: In multifocal breast cancers, additional lesions detected on MRI and second-look US have the same or less invasive histopathology compared to the index lesion.

The short-term effects of CGRP monoclonal antibodies on bone turnover: A prospective cohort study.

BACKGROUND: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) are an effective treatment of migraine however may have possible off-target effects. Pre-clinical studies implicate CGRP in several aspects of bone turnover and homeostasis. The clinical effect of CGRP mAb on bone turnover is not known, however. METHODS: Between June 2021 and July 2022, a multi-centre prospective cohort study was undertaken with eligible patients undergoing paired testing of the validated bone turnover markers procollagen type I N-terminal propeptide (P1NP) and serum C-terminal telopeptide of type I collagen (CTX) prior to and at least three months following administration of a CGRP mAb. RESULTS: A total of 45 patients with a mean age of 41.8 (SD 11.9) were included in the final analysis, all of whom received a ligand-targeting CGRP mAb. Administration of a CGRP mAb was associated with a statistically significant increase in P1NP from 44.5 microg/L to 51.5 microg/L (p = 0.004), but no significant change in CTX. CONCLUSION: In otherwise homeostatic conditions, short-term administration of a CGRP mAb is associated with increased P1NP, a bone formation marker but not with increased CTX, a bone resorption marker. Further study is required to validate these findings over longer time periods, in a larger cohort, and in pre-existing states of increased calcium stress and bone-turnover.

Cytokines in primary headache disorders: a systematic review and meta-analysis.

BACKGROUND: The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to synthesise the results of studies comparing peripheral blood cytokine levels between patients with migraine, tension-type headache, cluster headache, or new daily persistent headache (NDPH), and healthy controls; and in migraine between the ictal and interictal stages. METHODS: We searched PubMed/Medline and Embase from inception until July 2022. We included original research studies which measured unstimulated levels of any cytokines in peripheral blood using enzyme-linked immunosorbent assay or similar assay. We assessed risk of bias using the Newcastle-Ottawa Quality Assessment Scale. We used random effects meta-analysis with inverse variance weighted average to calculate standardised mean difference (SMD), 95% confidence intervals, and heterogeneity for each comparison. This study is registered with PROSPERO (registration number CRD42023393363). No funding was received for this study. RESULTS: Thirty-eight studies, including 1335 patients with migraine (32 studies), 302 with tension-type headache (nine studies), 42 with cluster headache (two studies), and 1225 healthy controls met inclusion criteria. Meta-analysis showed significantly higher interleukin (IL)-6 (SMD 1.07, 95% CI 0.40-1.73, p = 0.002), tumour necrosis factor (TNF)-α (SMD 0.61, 95% CI 0.14-1.09, p = 0.01), and IL-8 (SMD 1.56, 95% CI 0.03-3.09, p = 0.04), in patients with migraine compared to healthy controls, and significantly higher interleukin-1ß (IL-1ß) (SMD 0.34, 95% CI 0.06-0.62, p = 0.02) during the ictal phase of migraine compared to the interictal phase. Transforming growth factor (TGF)-ß (SMD 0.52, 95% CI 0.18-0.86, p = 0.003) and TNF-α (SMD 0.64, 95% CI 0.33-0.96, p = 0.0001) were both higher in patients with tension-type headache than controls. CONCLUSIONS: The higher levels of the proinflammatory cytokines IL-6, IL-8 and TNF-α in migraine compared to controls, and IL-1ß during the ictal stage, suggest a role for inflammation in the pathophysiology of migraine, however prospective studies are required to confirm causality and investigate the mechanisms for the increase in cytokine levels identified. Cytokines may also have a role in tension-type headache. Due a lack of data, no conclusions can be made regarding cluster headache or NDPH.

Autonomic symptoms in migraine: Results of a prospective longitudinal study.

Objective: To assess the prevalence and burden of autonomic symptoms in migraine, and determine the relationship with migraine frequency. Background: Autonomic symptoms in migraine have been theorized to occur in the setting of inter-ictal sympathetic hypoactivity and hyper-sensitivity. There is limited data prospectively assessing cranial and extra-cranial autonomic symptoms with a validated instrument, or longitudinal data on the relationship between migraine disease activity and autonomic symptoms. Methods: Patients attending a single tertiary academic center were recruited into a prospective cohort study between September 2020 and June 2022. In addition to standard clinical care, they completed several surveys including the Composite Autonomic Symptom Scale (COMPASS-31) questionnaire, a validated survey of autonomic symptoms. Results: A total of 43 patients (66.7% female, median age 42, IQR 17) were included in the final analysis. There was a baseline 20 monthly headache days (MHD) (IQR 21.7), and 65.1% of the population had chronic migraine by ICHD-3 criteria. A significantly elevated weighted COMPASS-31 score was reported in 60.5% of respondents (mean 30.3, SD 13.3) at baseline. After 12 months treatment, significant improvements were reported in migraine frequency (median MHD 20-8.7) and disability (median Migraine Disability Assessment Score 67-48), but not in autonomic symptoms (mean score 30.3, SD 11.2). Conclusion: Autonomic symptoms were frequently reported in patients with migraine. However, they did not correlate with headache frequency or reversion to episodic frequency. Further study is required to elucidate specific approaches and treatments for autonomic symptoms, and further evaluate the underlying pathophysiological mechanisms.

Imaging in headache disorders.

Patients with a suspected change in intracranial pressure or a trigeminal autonomic cephalgia require MRI. The need for investigation for other headache disorders is guided by the clinical evaluation of the patient. Particular care should be taken to identify any 'red flags'. Incidental findings on MRI occur in approximately 2% of patients. Patients with migraine have an increased rate of white matter lesions, but these are of uncertain clinical significance.

The prevalence of headache disorders in Postural Tachycardia Syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking. OBJECTIVES: To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options. METHODS: Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome. RESULTS: Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified.Limitations: Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results. CONCLUSIONS: Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies.

Cluster headache in adults.

Cluster headache is characterised by attacks of very severe, unilateral headache lasting 15-180 minutes, up to eight times per day. The attacks are associated with cranial autonomic symptoms on the same side and a sense of agitation or restlessness First-line acute abortive treatments include intranasal or subcutaneous sumatriptan or high-flow oxygen. Neuromodulation may benefit some patients First-line preventive therapy is high-dose verapamil. Close monitoring is required for the adverse effect of arrhythmia There are several emerging therapies that have either proven efficacy, or possible benefit for cluster headache. They include drugs aimed at the calcitonin gene-related peptide.

Intravenous Lidocaine and Ketamine Infusions for Headache Disorders: A Retrospective Cohort Study.

Introduction: The use of lidocaine (lignocaine) and ketamine infusion in the inpatient treatment of patients with headache disorders is supported by small case series. We undertook a retrospective cohort study in order to assess the efficacy, duration and safety of lidocaine and ketamine infusions. Methods: Patients admitted between 01/01/2018 and 31/07/2021 were identified by ICD code and electronic prescription. Efficacy of infusion was determined by reduction in visual analog score (VAS), and patient demographics were collected from review of the hospital electronic medical record. Results: Through the study period, 83 infusions (50 lidocaine, 33 ketamine) were initiated for a headache disorder (77 migraine, three NDPH, two SUNCT, one cluster headache). In migraine, lidocaine infusion achieved a ≥50% reduction in pain in 51.1% over a mean 6.2 days (SD 2.4). Ketamine infusion was associated with a ≥50% reduction in pain in 34.4% over a mean 5.1 days (SD 1.5). Side effects were observed in 32 and 42.4% respectively. Infusion for medication overuse headache (MOH) led to successful withdrawal of analgesia in 61.1% of lidocaine, and 41.7% of ketamine infusions. Conclusion: Lidocaine and ketamine infusions are an efficacious inpatient treatment for headache disorders, however associated with prolonged length-of-stay and possible side-effects.

The state of migraine: An update on current and emerging treatments.

BACKGROUND: Migraine is a common neurological disorder, affecting one in seven people, and is the second leading cause of disability worldwide. OBJECTIVE: The aim of this article is to summarise the diagnosis, pathophysiology and treatment of migraine. DISCUSSION: Key to limiting the disability of migraine and progression to chronic migraine is addressing modifiable risk factors, including implementing effective preventive treatment and avoiding overuse of acute treatment. In this article, the authors review strategies for effective acute and preventive treatment of migraine and introduce the new treatments of migraine targeting calcitonin gene-related peptide signalling.

Inflammatory complications of CGRP monoclonal antibodies: a case series.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

OnabotulinumtoxinA in Migraine: A Review of the Literature and Factors Associated with Efficacy.

The efficacy of onabotulinumtoxinA (OnaB-A) as a preventative treatment for chronic migraine, emerging fortuitously from clinical observation is now supported by class one evidence and over two decades of real-world clinical data. There is still limited ability to predict a clinically meaningful response to OnaB-A for individual patients, however. This review summarises briefly the proposed mechanism of OnaB-A in chronic migraine, the literature of predictors of clinical response, and recent developments in the field.

Exciting fluorescence compounds on an optical fiber's side surface with a liquid core waveguide.

A new fiber optic fluorescence spectroscopic method using a liquid core waveguide (LCW) as an excitation element has been developed for detecting a fluorescence compound absorbed on an optical fiber's surface. A laser light beam was coupled into a multimode optical fiber. The distal end of the fiber was inserted into an LCW. The diverging light emerging from the fiber's end was collected and guided within the LCW. A tapered optical fiber was inserted into the LCW from the other side. Laser light traveling in the LCW evenly illuminates the tapered fiber surface and excites fluorescence molecules absorbed on the tapered fiber's surface. Fluorescence light emitted from the tapered fiber surface was collected with the fiber itself and delivered through the fiber to an optical fiber compatible spectrometer for detection. This new technique provides an efficient way for evenly exciting fluorescence compounds absorbed on an optical fiber's surface.